The most important requirement is that you first obtain local research ethics committee approval. Because the trial has Multicentre Research Ethics Committee approval in the UK, applying for local research ethics committee approval in the UK should be much simpler. The CRASH Co-ordinating Centre can help you with your application. If you would like help, please provide the information shown below.  We will then send you the CRASH Collaborator’s pack that has everything you need for your ethics committee application in the UK.

Because the doctors and nurses collaborating in the CRASH trial are busy, and working in emergency situations, the trial involves them in almost no extra work: no special investigations or changes to usual management are required, and data collection is absolutely minimal. In-hospital deaths, complications and short-term recovery are recorded on a one page, single sided early outcome form that can be completed entirely from the hospital notes. Long-term recovery is assessed at six months by staff at the CRASH co-ordinating centre and will not involve any additional work for collaborating hospitals in the UK. The National Co-ordinators in collaborating countries will be asked to send out postal questionnaires or conduct brief telephone interviews with patients at six months after injury.

The MRC fully accepts responsibility attached to its sponsorship of the CRASH Trial, and as such, would give sympathetic consideration to claims for any non-negligent harm suffered by anyone as a result of participating in this trial.

If a relative is present when a patient is being considered for trial entry, and the relative objects to the patient being in the trial, the patient should not be entered. If a relative arrives in hospital after a patient has been enrolled, and objects to the patient being in the trial, an urgent meeting is arranged with a senior clinician to discuss the trial, and if the relative still objects, the trial treatment should be stopped.patient being enrolled in the trial?

Patients with head injury and impaired consciousness are eligible for inclusion in the CRASH Trial if the responsible doctor is substantially uncertain as to the appropriateness of steroids in a particular patient.  The question of whether the impaired consciousness in a head injured patient who has been drinking or using drugs is attributable to the head injury or to substance use is a matter of judgement for the responsible clinician.  Hence, judgements about both the impaired consciousness and about the appropriateness of steroids are relevant when considering the enrolment of a patient.  If the responsible doctor is substantially certain that an intoxicated patient with head injury will not benefit from steroids they should not be entered into the trial. However, all those for whom the responsible doctor is substantially uncertain as to whether or not to give corticosteroids are eligible for randomisation, and as many such patients as possible should be considered for the trial.  By way of example:

(i) an intoxicated young man fell over in a pub and has a scalp laceration; the clinician believes that the patient's impaired consciousness is most likely due to inebriation, that the likelihood of serious brain injury is minimal, and that use of steroids would be inappropriate.  The patient should not be entered into the trial.

(ii) a young man who has been drinking heavily drives his car into a wall at high speed, is unconscious, and has a severe head injury.  Irrespective of the evidence of intoxication the doctor is substantially uncertain about whether steroids would benefit her patient, and therefore enrols him in the CRASH trial.

We expect that a large proportion of the patients eligible for inclusion in the CRASH Trial will have multiple injuries. If the responsible doctor is uncertain as to the appropriateness of steroids in these patients they should be included in the trial.

This short term corticosteroid regimen should not cause serious gastrointestinal bleeding. The decision whether to exclude a patient because of a history of gastro-intestinal bleeding is the responsibility of the individual patient’s doctor.

No. An Outcome Form should be completed for all patients who are randomised, irrespective of whether the treatment was actually given or if only part of the treatment (eg. loading dose only) was given. This is necessary to ensure complete and unbiased follow-up of all trial participants.

In general there should be no need to unblind the allocated treatment. If some contra-indication to corticosteroids develops after randomisation (e.g. severe gastro-intestinal bleeding), the trial treatment should simply be stopped. Unblinding was never found to be necessary in the NASCIS trial of MP in spinal cord injury,4 and should be done only in those rare cases when the doctor believes that clinical management depends importantly upon knowledge of whether the patient received corticosteroid or placebo (e.g. suspected anaphylaxis). In those few cases when urgent unblinding is considered necessary, the randomisation service should be telephoned, giving the name of the doctor authorising unblinding and the CRASH treatment pack number (if available), and the caller will then be told whether the patient received corticosteroid or placebo.

The trial co-ordinators will know the levels of supplies in each hospital and will ensure that adequate supplies of treatment packs are maintained at all times. However, if trial materials, appear to be running low then additional stock can be obtained from the CRASH Co-ordinating Office.

Head injured patients aged 16 or older who – in the absence of sedation – are observed whilst in hospital to have a GCS of 14 or less may be eligible for enrolment in the CRASH trial, if the responsible clinician is substantially uncertain about the appropriateness of steroids.  This means that the patient’s head injury is such that consciousness would be (or would likely have been) impaired even in the absence of the sedating agent.  (Sedating agents could include prescribed drugs (e.g., morphine), legal sedatives not requiring prescription (e.g., alcohol), and illicit substances (e.g., heroin).

The question of whether the impaired consciousness in a head injured patient who is also sedated is attributable to the head injury or solely to a sedating agent is a matter of judgement for the responsible clinician.  Hence, judgements about both the cause of impaired consciousness and about the appropriateness of steroids are relevant when considering the enrolment of a patient.  If the responsible doctor is substantially certain that a sedated patient with head injury will not benefit from steroids they should not be entered into the trial.  However, all those for whom the responsible doctor is substantially uncertain as to whether or not to give corticosteroids are eligible for randomisation, and as many such patients as possible should be considered for the trial.

Examples (see also examples under Query X above): 1. A patient with a severe head injury received sedation prior to performance of a head CT scan.  In the opinion of the responsible doctor, the patient’s head injury is sufficient to cause impaired consciousness even in the absence of sedation.  The clinician is uncertain about the appropriateness of corticosteroids, and decides to enrol the subject in the trial.

2. A patient with a mild head injury was sedated prior to the setting of his femur fracture.  The responsible clinician judges that without sedation, the patient’s GCS would have been fully conscious, hence the patient is not eligible for the trial.

No. Patients should be discharged as soon as they are ready. If this is before the end of the trial infusion, the infusion should simply be stopped.

17. What should we do with any unused trial treatment vials?

Any unused trial treatment should be destroyed.

18. What if the infusion is interrupted?

Resume as soon as possible. The infusion is stable for 24 hours, after which the bag should be discarded regardless of total volume infused.

19. What if the patient is transferred to another hospital after being randomised but before the 48 hour infusion is completed.

Please ensure the allocated treatment pack accompanies the patient to the transferring ospital. This contains all the instructions for administration of the trial drug and trial procedures. With this send one of the early outcome forms (with box and pack sticker attached). Complete the remaining form and send to the MRC CRASH Trial Centre. Ensure a HOSPITAL TRANSFER FORM travels to the transferring hospital with the patient. This should stop queries regarding the trial returning to you!

20. What if the patient is transferred to another hospital after the infusion is completed but within 14 days of admission.

Please send one of the 14 day outcome forms with the patient. Complete the other 14 day outcome form, specifying the name if it is an acute care hospital, and send to the MRC Trial Centre.

NB. Ensure the HOSPITAL TRANSFER FORM travels to the transferring hospital with the patient.